{"title":"VEGF165b 突变体可用作蛋白载体,与 Mucin1 肽形成嵌合肿瘤疫苗,从而激发抗肿瘤反应","authors":"","doi":"10.1016/j.molimm.2024.09.009","DOIUrl":null,"url":null,"abstract":"<div><p>Peptide-based anticancer vaccines have shown some efficacy in generating cancer-specific immune responses in various cancer studies, but clinical success is limited, one of the reasons is due to its prone degradation and weak immunogenicity. So some tumor epitope peptide vaccines often require coupling or forming fusion proteins with corresponding protein carriers to enhance their stability and immunogenicity. Given the scarcity of validated carriers for clinical trials, there is an urgent requirement for the development of novel protein carrier. Our previous work has demonstrated that VEGF165b mutant could be used as an effective immunization adjunct to enhance anti-tumor immune response. By analyzing and evaluating the gene structure of VEGF, we speculated that mVEGF165b has the potential to be utilized as a tumor peptide vaccine carrier. An mVEGF165b-MUC1 chimeric tumor vaccine was produced by fusing the MUC1 peptide ((MUC1, a T-cell epitope dominant peptide from Mucin1) to the C-terminus of mVEGF165b, expressing the fusing protein in pichia yeast, followed by purification with a HiTrap heparin affinity chromatography column. We found that immunizing mice with mVEGF165b-MUC1 fusion protein induced high-titer antibodies against VEGF in a preventive context, which in turn reduced the proportion of Tregs and further stimulated mice to produce T-cell responses specific to mucin1. The high-titer VEGF antibody stimulated by mVEGF165b also promoted tumor blood vessel maturation and facilitated T-cell infiltration. In conclusion,immunized with mVEGF165b-MUC1 protein are beneficial for eliciting immune responses targeting Mucin1, mVEGF165b have the potential to be utilized as a peptide tumor vaccine carrier.</p></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":null,"pages":null},"PeriodicalIF":3.2000,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"VEGF165b mutant can be used as a protein carrier to form a chimeric tumor vaccine with Mucin1 peptide to elicit an anti-tumor response\",\"authors\":\"\",\"doi\":\"10.1016/j.molimm.2024.09.009\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Peptide-based anticancer vaccines have shown some efficacy in generating cancer-specific immune responses in various cancer studies, but clinical success is limited, one of the reasons is due to its prone degradation and weak immunogenicity. So some tumor epitope peptide vaccines often require coupling or forming fusion proteins with corresponding protein carriers to enhance their stability and immunogenicity. Given the scarcity of validated carriers for clinical trials, there is an urgent requirement for the development of novel protein carrier. Our previous work has demonstrated that VEGF165b mutant could be used as an effective immunization adjunct to enhance anti-tumor immune response. By analyzing and evaluating the gene structure of VEGF, we speculated that mVEGF165b has the potential to be utilized as a tumor peptide vaccine carrier. An mVEGF165b-MUC1 chimeric tumor vaccine was produced by fusing the MUC1 peptide ((MUC1, a T-cell epitope dominant peptide from Mucin1) to the C-terminus of mVEGF165b, expressing the fusing protein in pichia yeast, followed by purification with a HiTrap heparin affinity chromatography column. We found that immunizing mice with mVEGF165b-MUC1 fusion protein induced high-titer antibodies against VEGF in a preventive context, which in turn reduced the proportion of Tregs and further stimulated mice to produce T-cell responses specific to mucin1. The high-titer VEGF antibody stimulated by mVEGF165b also promoted tumor blood vessel maturation and facilitated T-cell infiltration. In conclusion,immunized with mVEGF165b-MUC1 protein are beneficial for eliciting immune responses targeting Mucin1, mVEGF165b have the potential to be utilized as a peptide tumor vaccine carrier.</p></div>\",\"PeriodicalId\":18938,\"journal\":{\"name\":\"Molecular immunology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2024-09-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0161589024001792\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular immunology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0161589024001792","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
在各种癌症研究中,多肽类抗癌疫苗在产生癌症特异性免疫反应方面显示出一定的疗效,但临床成功率有限,原因之一是其易降解和免疫原性弱。因此,一些肿瘤表位肽疫苗往往需要与相应的蛋白载体偶联或形成融合蛋白,以增强其稳定性和免疫原性。鉴于用于临床试验的有效载体的稀缺性,新型蛋白载体的开发迫在眉睫。我们之前的工作已经证明,VEGF165b 突变体可作为一种有效的免疫辅助剂来增强抗肿瘤免疫反应。通过分析和评估血管内皮生长因子的基因结构,我们推测 mVEGF165b 有潜力用作肿瘤多肽疫苗载体。我们将 MUC1 多肽(MUC1 是来自 Mucin1 的 T 细胞表位优势肽)与 mVEGF165b 的 C 端融合,制成了 mVEGF165b-MUC1 嵌合肿瘤疫苗。与 mVEGF165b 的 C 末端融合,在毕赤酵母中表达融合蛋白,然后用 HiTrap 肝素专用色谱柱纯化。我们发现,用 mVEGF165b-MUC1 融合蛋白免疫小鼠可诱导高滴度的血管内皮生长因子抗体,从而降低 Treg 的比例,并进一步刺激小鼠产生针对粘蛋白 1 的特异性 T 细胞反应。由 mVEGF165b 激发的高滴度血管内皮生长因子抗体还能促进肿瘤血管成熟,并促进 T 细胞浸润。总之,用mVEGF165b-MUC1蛋白免疫有利于激发针对Mucin1的免疫反应,mVEGF165b有可能被用作多肽肿瘤疫苗载体。
VEGF165b mutant can be used as a protein carrier to form a chimeric tumor vaccine with Mucin1 peptide to elicit an anti-tumor response
Peptide-based anticancer vaccines have shown some efficacy in generating cancer-specific immune responses in various cancer studies, but clinical success is limited, one of the reasons is due to its prone degradation and weak immunogenicity. So some tumor epitope peptide vaccines often require coupling or forming fusion proteins with corresponding protein carriers to enhance their stability and immunogenicity. Given the scarcity of validated carriers for clinical trials, there is an urgent requirement for the development of novel protein carrier. Our previous work has demonstrated that VEGF165b mutant could be used as an effective immunization adjunct to enhance anti-tumor immune response. By analyzing and evaluating the gene structure of VEGF, we speculated that mVEGF165b has the potential to be utilized as a tumor peptide vaccine carrier. An mVEGF165b-MUC1 chimeric tumor vaccine was produced by fusing the MUC1 peptide ((MUC1, a T-cell epitope dominant peptide from Mucin1) to the C-terminus of mVEGF165b, expressing the fusing protein in pichia yeast, followed by purification with a HiTrap heparin affinity chromatography column. We found that immunizing mice with mVEGF165b-MUC1 fusion protein induced high-titer antibodies against VEGF in a preventive context, which in turn reduced the proportion of Tregs and further stimulated mice to produce T-cell responses specific to mucin1. The high-titer VEGF antibody stimulated by mVEGF165b also promoted tumor blood vessel maturation and facilitated T-cell infiltration. In conclusion,immunized with mVEGF165b-MUC1 protein are beneficial for eliciting immune responses targeting Mucin1, mVEGF165b have the potential to be utilized as a peptide tumor vaccine carrier.
期刊介绍:
Molecular Immunology publishes original articles, reviews and commentaries on all areas of immunology, with a particular focus on description of cellular, biochemical or genetic mechanisms underlying immunological phenomena. Studies on all model organisms, from invertebrates to humans, are suitable. Examples include, but are not restricted to:
Infection, autoimmunity, transplantation, immunodeficiencies, inflammation and tumor immunology
Mechanisms of induction, regulation and termination of innate and adaptive immunity
Intercellular communication, cooperation and regulation
Intracellular mechanisms of immunity (endocytosis, protein trafficking, pathogen recognition, antigen presentation, etc)
Mechanisms of action of the cells and molecules of the immune system
Structural analysis
Development of the immune system
Comparative immunology and evolution of the immune system
"Omics" studies and bioinformatics
Vaccines, biotechnology and therapeutic manipulation of the immune system (therapeutic antibodies, cytokines, cellular therapies, etc)
Technical developments.